Motorized spiral enteroscopy: results of an international multicenter prospective observational clinical study in patients with normal and altered gastrointestinal anatomy.

BACKGROUND : Motorized spiral enteroscopy (MSE) has been shown to be safe and effective for deep enteroscopy in studies performed at expert centers with limited numbers of patients without previous abdominal surgery. This study aimed to investigate the safety, efficacy, and learning curve associated with MSE in a real-life scenario, with the inclusion of patients after abdominal surgery and with altered anatomy. METHODS : Patients with indications for deep enteroscopy were enrolled in a prospective observational multicenter study. The primary objective was the serious adverse event (SAE) rate; secondary objectives were the diagnostic and therapeutic yield, procedural success, time, and insertion depth. Data analysis was subdivided into training and core (post-training) study phases at centers with different levels of MSE experience. RESULTS : 298 patients (120 women; median age 68, range 19-92) were enrolled. In the post-training phase, 21.5 % (n = 54) had previous abdominal surgery, 10.0 % (n = 25) had surgically altered anatomy. Overall, SAEs occurred in 2.3 % (7/298; 95 %CI 0.9 %-4.8 %). The SAE rate was 2.0 % (5/251) in the core group and 4.3 % (2/47) in the training group, and was not increased after abdominal surgery (1.9 %). Total enteroscopy was achieved in half of the patients (n = 42) undergoing planned total enteroscopy. In 295/337 procedures (87.5 %), the anatomical region of interest could be reached. CONCLUSIONS : This prospective multicenter study showed that MSE was feasible and safe in a large cohort of patients in a real-life setting, after a short learning curve. MSE was shown to be feasible in postsurgical patients, including those with altered anatomy, without an increase in the SAE rate.

Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case-control study.

Background and study aims The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER. Patients and methods All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal [GI] endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI). Results A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m2) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %. Conclusion Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.

Gene Expression in the Liver Remnant Is Significantly Affected by the Size of Partial Hepatectomy: An Experimental Rat Study.

Extended hepatectomies may result in posthepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy (PH). Thirty Wistar rats were subjected to 30%, 70%, or 90% PH, sham operation, or no operation. Twenty-four hours following resection, liver tissue was harvested and genome-wide expression analysis was performed. Cluster analysis revealed two main groupings, one containing the PH(90%) and one containing the remaining groups [baseline, sham, PH(30%), and PH(70%)]. Categorization of specific affected molecular pathways in the PH(90%) group revealed a downregulation of cellular homeostatic function degradation and biosynthesis, whereas proliferation, cell growth, and cellular stress and injury were upregulated in the PH(90%) group. After PH(90%), the main upregulated pathways were mTOR and ILK. The main activated upstream regulators were hepatocyte growth factor and transforming growth factor. With decreasing size of the future liver remnant, the liver tended to prioritize expression of genes involved in cell proliferation and differentiation at the expense of genes involved in metabolism and body homeostasis. This prioritizing may be an essential molecular explanation for posthepatectomy liver failure.

Long-term outcome of peroral endoscopic myotomy for esophageal achalasia in patients with previous Heller myotomy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging procedure in the treatment of esophageal achalasia, a primary motility disorder. However, the long-term outcome of POEM in patients, who have previously undergone a Heller myotomy, is unknown. METHODS: Using a local database, we identified patients with esophageal achalasia, who underwent POEM. We compared patients with a previous Heller myotomy to those, who had received none or only non-surgical therapy prior to the POEM procedure. We conducted follow-up examinations at 3, 12, and 24 months following the procedure. RESULTS: We included 66 consecutive patients undergoing POEM for achalasia, of which 14 (21.2 %) had undergone a prior Heller myotomy. In both groups, the preoperative Eckardt score was 7. Postoperatively, the non-Heller group experienced a more pronounced symptom relief at both 3-, 12-, and 24-month follow-up compared with the Heller group, and there was a tendency for the effect of POEM to reduce over time. We suggest that there is a correlation between preoperative measurements of gastroesophageal sphincter pressures and the chance of a successful POEM. CONCLUSIONS: POEM has a place in the treatment of esophageal achalasia in patients with a prior Heller myotomy and persistent symptoms as it is a safe procedure with acceptable long-term results.

Peroral endoscopic myotomy (POEM) for nutcracker esophagus. Three cases with 12 months follow-up.

INTRODUCTION: Peroral endoscopic myotomy (POEM) has been introduced as a new treatment of achalasia, and studies are emerging on POEM treatment of other esophageal motility disorders. The effects of medical treatment, botox injections and dilatations are often limited in patients with severe nutcracker esophagus (NE). We therefore decided to perform POEM in three patients with severe NE. MATERIAL AND METHODS: Informed consent was provided. POEM was performed under general anesthesia on the distal esophagus and upper stomach. At 3 months, 6 months and 1 year postoperatively all patients had clinical follow-up, barium swallow and high-resolution manometry. RESULTS: All patients displayed marked improvement with a significant reduction in Eckardt score at follow-up after 1 year, from 10, 10 and 11 to 3, 1 and 1, respectively. During follow-up, the patients were diagnosed with increased reflux index and one patient was diagnosed with gastroparesis. CONCLUSION: Considering our results, treating severe NE with POEM has to be considered in the future; however, further studies have to confirm this.

[Concurrent achalasia and severe obesity].

Achalasia is a rare oesophageal motility disorder which classically is not associated with obesity. We present the case of a 50-year-old woman who underwent gastric bypass and afterwards was diagnosed with achalasia. Following, she was treated successfully with peroral endoscopic myotomy (POEM). A thorough medical history revealed that symptoms of achalasia had been present for 25 years and were the cause of inappropriate eating habits and consequently morbid obesity. This case story illustrates the importance of being aware of simultaneous occurrence of achalasia and morbid obesity. Furthermore, it demonstrates that POEM is safe and effective for symptomatic relief of achalasia after previous gastric bypass.

[Presentation, diagnosis and management of swallowed foreign bodies]. / Præsentation, diagnose og håndtering af slugte fremmedlegemer.

Foreign body ingestion occurs commonly. In 80-90% of cases, the ingested foreign body passes uneventfully through the gastrointestinal tract; endoscopy is performed in 20% of cases, and surgery in less than 1%. Complications usually occur when the ingested foreign body is sharp, large, a button battery or multiple magnets. We present a potential algorithm for the management of swallowed foreign bodies. Most patients can be treated conservatively by observation alone, but often it is convenient to proceed to endoscopic retrieval. Surgery is reserved for complicated cases.

Detection of colorectal cancer in symptomatic outpatients without visible rectal bleeding: Validity of the fecal occult blood test.

BACKGROUND: In 2002, a new diagnostic strategy in symptomatic outpatients without known established colorectal cancer risk factors aged 40 years or older was implemented in Denmark. Fecal occult blood test (Hemoccult Sensa®) was a part of that strategy in patients without visible rectal bleeding. AIMS: The aim was to assess the validity of the Hemoccult Sensa® test in detecting colorectal cancer in the above-mentioned outpatients. PATIENTS: Symptomatic outpatients without known established colorectal cancer risk factors and without visible rectal bleeding. METHODS: Hemoccult Sensa® was performed before endoscopic examination. Colorectal cancer was identified at histopathological examination. Patients completed a questionnaire about their symptoms before their first hospital appointment. RESULTS: Eight of 256 patients were found to have colorectal cancer. Median patient age was 63 years. The positive predictive value, negative predictive value, sensitivity, and specificity of Hemoccult Sensa® for colorectal cancer were 10.5% (95% confidence interval [CI]: 6.8-14.3), 99.0% (95% CI: 97.8-100.0), 75.0% (95% CI: 69.7-80.3), and 79.4% (95% CI: 74.5-84.4). CONCLUSIONS: Hemoccult Sensa® as the initial examination in symptomatic outpatients without known established colorectal cancer risk factors presenting without rectal bleeding has to be used with caution. We did not find Hemoccult Sensa® test to be an acceptable alternative to flexible sigmoidoscopy.

Sensitive digital quantification of DNA methylation in clinical samples.

Analysis of abnormally methylated genes is increasingly important in basic research and in the development of cancer biomarkers. We have developed methyl-BEAMing technology to enable absolute quantification of the number of methylated molecules in a sample. Individual DNA fragments are amplified and analyzed either by flow cytometry or next-generation sequencing. We demonstrate enumeration of as few as one methylated molecule in approximately 5,000 unmethylated molecules in DNA from plasma or fecal samples. Using methylated vimentin as a biomarker in plasma samples, methyl-BEAMing detected 59% of cancer cases. In early-stage colorectal cancers, this sensitivity was four times more than that obtained by assaying serum-carcinoembryonic antigen (CEA). With stool samples, methyl-BEAMing detected 41% of cancers and 45% of advanced adenomas. In addition to diagnostic and prognostic applications, this digital quantification of rare methylation events should be applicable to preclinical assessment of new epigenetic biomarkers and quantitative analyses in epigenetic research.

[Danish National Guidelines for diagnostic strategy of patients with colorectal cancer symptoms]. / Følg de nationale retningslinjer ved mistanke om kolorektal cancer.

Danish National Guidelines (DNG) for diagnostic strategy of patients with colorectal cancer (CRC) symptoms are structured to ensure prompt and specific diagnostic testing, thus minimizing treatment delay. DNG state that the function of the general practitioner is to refer patients to a specialist as soon as the patient presents with CRC symptoms. Unfortunately, 60% of CRC patients experience a delay in referrals due to the fact that the guidelines are not followed as exemplified in our two cases.

Evaluation of the Danish national strategy for selective use of colonoscopy in symptomatic outpatients without known risk factors for colorectal cancer.

OBJECTIVE: A diagnostic strategy implemented in Denmark in 2002 recommends selective use of colonoscopy in outpatients without known colorectal cancer (CRC) risk factors who are referred with symptoms consistent with possible CRC. Selection of patients for colonoscopy was based on the presenting symptom(s) and findings at the initial examination (flexible sigmoidoscopy/faecal occult blood test). The aim of this study was to evaluate the strategy by assessing the prevalence of patients with diagnosed CRC, the frequency of patients with missed CRC, the adherence to the strategy and the number of examinations performed. MATERIAL AND METHODS: We prospectively studied patients aged 40 years and older without known risk factors for CRC, referred to two surgical outpatient clinics during a period of 15-16 months. Examinations, findings at the examinations, the final diagnoses and date of discharge were recorded. Missed CRCs were identified by follow-up in hospital discharge registries. RESULTS: CRC was diagnosed in 126 (5.3%; 95% CI: 4.5-6.3%) of the 2361 patients included during the diagnostic work-up. Two additional cancers identified at follow-up were both missed during colonoscopy (1.5%; 95% CI: 0.2-5.4%). The adherence to the strategy was 75.7%, and 125 of the 126 patients with a CRC were examined in conformity with the recommended strategy. Almost 60% of the patients underwent colonoscopy and almost 50% underwent both flexible sigmoidoscopy and colonoscopy. CONCLUSIONS: The diagnostic strategy is an acceptable alternative to initial colonoscopy, with a low probability of missing a CRC; however, a considerable proportion of the patients undergo colonoscopy and multiple examinations.

[Diagnostic strategy with respect to symptoms of colorectal cancer]. / Diagnostisk strategi ved symptomer på kolorektal cancer.

In relation to the risk of colorectal cancer, the population is divided into high-risk and average-risk groups. Patients at high risk are followed according to the national recommendations. Patients at average risk are examined according to their primary symptom(s). The strategy is based on the diagnostic strategy described in a Danish Health Technology Assessment published in 2001. The article states the recommendations for the high- risk groups and describes the value of the individual primary symptoms of colorectal cancer for average-risk patients and the examinations recommended accordingly.